Renal failure is a life-threatening and costly medical condition. End-stage renal disease, defined as severe renal dysfunction requiring chronic dialysis or kidney transplantation, is increasing in prevalence and has an annual mortality rate exceeding 20%. Less severe loss of renal function also has important health consequences. Mild to moderate reductions in renal function and microalbuminuria are important predictors of cardiovascular disease and death, in high-risk groups as well as in the general population. The risk of adverse outcomes increases with decreasing renal function. Even in the absence of known risk factors for renal function decline, such as hypertension or diabetes, kidney dysfunction may develop slowly over decades. Slowing or preventing decline in renal function may favorably impact morbidity and mortality. Genetic factors, biological processes (such as inflammation) and environmental factors (such as analgesic use) may contribute to renal function decline. Heightened activity of the renin-angiotensin system (RAS), particularly of angiotensin II, is an important mediator of renal pathophysiology. Thus, genes related to the RAS system may have important long-term effects on renal function. Chronic inflammation may adversely affect the kidney by causing vascular disease and fibrosis. Analgesics are the most commonly used drugs in the US, and chronic analgesic use may be an important, preventable cause of renal dysfunction. The primary objective of this study is to examine prospectively risk factors for renal function decline, defined as decline in estimated glomerular filtration rate (using serum creatinine) and development of microalbuminuria, among 5000 participants in two large female cohorts: the Nurses' Health Study I and the Nurses' Health Study II. Stored and newly collected blood and urine specimens will permit repeated measurements of renal function and urine albumin and will allow us to examine changes over a period of 19 years in NHS I and 11 years in NHS II. Mixed-effects regression will be used to analyze the slope of renal function in the exposed and unexposed groups during the long-term follow-up. This study will provide: 1) prospective data on risk factors for renal function decline; 2) threshold levels of safe cumulative dose of individual classes of analgesics; 3) population-based incidence rates of renal dysfunction and rate of renal function decline in younger and older women; and 4) an important resource for future long-term studies of renal function decline. ? ?
| Pattaro, Cristian (see original citation for additional authors) (2016) Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nat Commun 7:10023 |
| Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna et al. (2013) Common variants in Mendelian kidney disease genes and their association with renal function. J Am Soc Nephrol 24:2105-17 |
| Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander et al. (2012) Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genet 8:e1002584 |
| International Consortium for Blood Pressure Genome-Wide Association Studies (see original citation for additional authors) (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478:103-9 |
| Böger, Carsten A; Chen, Ming-Huei; Tin, Adrienne et al. (2011) CUBN is a gene locus for albuminuria. J Am Soc Nephrol 22:555-70 |
| Lin, Julie; Curhan, Gary C (2011) Associations of sugar and artificially sweetened soda with albuminuria and kidney function decline in women. Clin J Am Soc Nephrol 6:160-6 |
| Lin, Julie; Fung, Teresa T; Hu, Frank B et al. (2011) Association of dietary patterns with albuminuria and kidney function decline in older white women: a subgroup analysis from the Nurses' Health Study. Am J Kidney Dis 57:245-54 |
| Lin, J; Hu, F B; Mantzoros, C et al. (2010) Lipid and inflammatory biomarkers and kidney function decline in type 2 diabetes. Diabetologia 53:263-7 |
| Robinson, Emily S; Fisher, Naomi D; Forman, John P et al. (2010) Physical activity and albuminuria. Am J Epidemiol 171:515-21 |
| Lin, Julie; Hu, Frank B; Curhan, Gary C (2010) Associations of diet with albuminuria and kidney function decline. Clin J Am Soc Nephrol 5:836-43 |
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